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Use of p2x7 pathway for assessing the sensitivity of a subject to a cancer treatment

Inactive Publication Date: 2011-09-22
INSTITUT GUSTAVE ROUSSY +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0018]The present invention also concerns a method for increasing the efficacy of a chemotherapeutic or radiotherapeutic treatment in a subject suffering from a cancer and having a non-functional P2X7-elicited NALP3 inflammasome pathway, wherein

Problems solved by technology

However, one of the most important problems in cancer treatment remains that individual subjects with the same histology do not respond identically to a given agent or a given therapeutic protocol.
However, radiotherapy and some chemotherapeutic agents could also induce specific immune responses resulting in immunogenic cancer cell death or in immunostimulatory side effects (Koebel et al., 2007; Zitvogel et al., 2008).
Moreover, considering that most of anticancer treatments not only cause severe side effects but also are generally physically exhausting for patients and often associated with high costs, the choice of the appropriate chemotherapy and / or radiotherapy protocols is of capital importance.

Method used

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  • Use of p2x7 pathway for assessing the sensitivity of a subject to a cancer treatment
  • Use of p2x7 pathway for assessing the sensitivity of a subject to a cancer treatment
  • Use of p2x7 pathway for assessing the sensitivity of a subject to a cancer treatment

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[0173]Material and Methods

[0174]Mouse Strains

[0175]BALB / c (H-2d), C57BL / 6 (H-2b), nu / nu and Rag2− / − C57BL / 6 mice were obtained from the Centre d'élevage Janvier (Le Genest St Isle, France) and from Charles River Laboratories (L'Arbresle, France), as well as from Taconic (Denmark).

[0176]C57BL / 6 Ifnγr1− / −, Casp1− / −, Asc− / −, Nalp3− / −, P2X7− / −and IL-12Rβ2− / − mice were described in Huang et al, 1993; Li et al., 1995; Srinivasula et al., 2002; Kanneganti et al., 2006; Solle et al., 2001; and Wu et al., 2000, respectively. Mice were bred in pathogen-free conditions. Animals were used between 6 and 20 weeks of age. All animals were maintained according to both the FELASA guidelines and the Animal Experimental Ethics Committee Guidelines (Val de Marne, France).

[0177]Reagents and Materials

[0178]Cell death was induced either with doxorubicin, mitoxantrone (Sigma Aldrich, St Quentin Fallavier, France), or oxaliplatin (Sanofi-Aventis, France). Ovalbumin protein was purchased from Calbiochem (Dar...

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Abstract

The present invention concerns methods for assessing the sensibility of a subject to an anticancer treatment, for screening compounds which are useful for treating a cancer and for determining the likelihood of a metastatic relapse in a subject. The methods are based on the finding that a non-functional P2X7-elicited NALP3 inflammasome pathway in a subject is indicative of a resistance to treatment. The invention further concerns methods for treating a cancer and for restoring the sensitivity of the subject to a cancer treatment.

Description

FIELD OF THE INVENTION[0001]The present disclosure generally relates to the fields of genetics, immunology and medicine. The inventors more particularly disclose the identification of a pathway used to predict or assess the sensitivity of a subject to a treatment of cancer. This pathway can also be used for the screening of therapeutically active drugs and to restore the sensitivity.BACKGROUND OF THE INVENTION[0002]Cancer occurs when cell division gets out of control and results from impairment of a DNA repair pathway, the transformation of a normal gene into an oncogene or the malfunction of a tumor supressor gene.[0003]Along with surgery, chemotherapy and radiotherapy are used for treating many types of cancer. A large variety of chemotherapeutic agents, involving various mechanisms, has been developed and the survival of cancer patients has been greatly improved for many type of cancers. However, one of the most important problems in cancer treatment remains that individual subje...

Claims

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Application Information

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IPC IPC(8): A61K49/00C12Q1/02A61P35/00A61K38/20A61K38/02A61K38/12A61K39/395A61K38/21C12Q1/68C12Q1/37A61K33/243
CPCA61K31/551A61K31/704G01N2800/54G01N2800/52G01N2500/00G01N33/57407C12Q2600/156C12Q2600/136C12Q2600/106C12Q1/6886A61K45/06A61K38/212A61K38/2006A61K38/20A61K38/1709A61K38/12A61K33/24A61K2300/00A61P35/00A61P43/00A61K33/243
Inventor APETOH, LIONELTESNIERE, ANTOINEGHIRINGHELLI, FRANCOISZITVOGEL, LAURENCEKROEMER, GUIDO
Owner INSTITUT GUSTAVE ROUSSY
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